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PubMed1982

Inhibitory effect of phentolamine on diazepam-induced growth hormone secretion and lack of effect of diazepam on prolactin secretion in man.

Phentolamine, a postsynaptic noradrenergic (NA) receptor blocker, inhibits diazepam-induced growth hormone (GH) secretion in man. In order to study the effect of phentolamine on six healthy subjects with a diazepam (10 mg i.v.)-induced GH increase greater than 7.5 ng/ml, it was necessary to test 11 subjects. The six diazepam GH responders showed a significantly higher (p less than 0.01) GH stimulation after diazepam alone than after diazepam plus phentolamine (60 mg i.v.). The inhibitory effect of phentolamine suggests that NA alpha receptors are involved in the diazepam-induced GH increase. Prolactin secretion after administration of diazepam (10 mg i.v.) was only slightly elevated in comparison with placebo (i.v.), suggesting that diazepam does not have an agonistic effect on dopamine (DA) receptors.

Diazepam↗
PubMed1980

The use of levarterenol and phentolamine in patients with low cardiac output following open-heart surgery.

A study was made of the hemodynamic effects of levarterenol and phentolamine in patients in whom low cardiac output developed following open-heart operation. After the patients were weaned from cardiopulmonary bypass, the inotropic agents were infused into an external or internal jugular vein through an IVAC pump. Levarterenol was administered first until systolic arterial pressure rose 20 to 30% above the higest recorded preoperative pressure. After stabilization, phentolamine was administered, and infusion rates were adjusted so that arterial blood pressure was returned to levels measured before bypass. After infusion, all patients showed an increase in cardiac index, mean arterial pressure, mean stroke volume index, and left ventricular stroke work index. Mean pulmonary artery pressure, pulmonary vascular resistance, and left atrial pressure decreased in all patients. This study demonstrates that hemodynamic improvement occurs in humans in low cardiac output state with simultaneous infusion of levarterenol and phentolamine. We recommend these agents for use in patients with low output, unless they continue to receive propranolol during and after operation. Patients on a regimen of propranolol should not be given levarterenol and phentolamine.

Blood Pressure↗
PubMed1993

Urodynamic effects of intravesical instillation of atropine and phentolamine in patients with detrusor hyperactivity.

The effects of intravesical instillation of atropine (10(-6) M) and phentolamine (10(-6) M) on urodynamic parameters were investigated in patients with detrusor hyperactivity of neurogenic or non-neurogenic origin. A modified cystometric technique with slow intermittent filling was used. The reproducibility of the investigative procedure was first verified in 17 patients. Eighteen patients, 12 with detrusor hyperreflexia and 6 with detrusor instability, were then investigated with atropine and 17 patients, 11 with detrusor hyperreflexia and 6 with detrusor instability, were investigated with phentolamine. In individual patients clinically relevant improvements, such as an increased bladder capacity and a decreased detrusor pressure, were found. Five/12 neurogenic and 1/6 non-neurogenic patients responded to instillation of atropine. Five/11 neurogenic but none of the non-neurogenic patients responded to phentolamine. In the neurogenic group phentolamine caused an increase of the bladder capacity from 247 +/- 57 ml. to 378 +/- 57 ml. (p < 0.05). It is suggested that the different sensitivities to intravesical drug administration in patients with detrusor hyperreflexia and detrusor instability can be explained by pathophysiological differences and concluded that intravesical instillation of drugs may be of therapeutic value in selected groups of patients.

Administration, Intravesical↗
PubMed1987

Intracavernous self-injection with phentolamine and papaverine for the treatment of impotence.

To evaluate the efficacy and safety of intracavernous self-injection of phentolamine and papaverine for the treatment of impotence, 30 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled cross-over study of papaverine and phentolamine versus normal saline. A total of 29 patients completed the study. The phentolamine plus papaverine combination resulted in erection in 24 patients (82.8 per cent) and no erection occurred after injection of saline. Of the patients 12 (41.4 per cent) experienced technical difficulties with the injection. Ecchymosis of the penis at the site of injection was common and 1 patient experienced priapism that resolved spontaneously. No other side effects occurred. Intracavernous self-injection with phentolamine and papaverine appears to be a safe and effective treatment of impotence but long-term effects must be determined.

Aged↗
PubMed1986

Hemodynamics of papaverine- and phentolamine-induced penile erection.

We investigated the hemodynamic changes induced in the canine corpora cavernosa by intracorporeal injection of papaverine or phentolamine. In six dogs studied, papaverine profoundly increased the resistance to venous outflow, whereas phentolamine (an alpha-adrenergic blocker) had little or no effect. In four other dogs, flow within the internal pudendal artery was measured with an ultrasonic flow probe placed directly on the artery. Papaverine increased arterial flow by 300 to 700 per cent over baseline levels, whereas the increase with phentolamine was only 50 to 100 per cent. We conclude that papaverine, by virtue of its direct smooth-muscle-relaxing properties, has a dual hemodynamic effect: it decreases the resistance to arterial inflow, thereby allowing large increases in the flow of blood into the penis during tumescence; and increases the resistance to venous outflow. Phentolamine only decreases the resistance to arterial inflow, more modestly than papaverine, and does not increase the resistance to venous outflow.

Animals↗
PubMed2001

Combination of phentolamine and L-arginine or sildenafil synergistically improves neurogenic relaxation of rabbit corpus cavernosum smooth muscle.

OBJECTIVES: To analyze the effects of combining an alpha-adrenergic receptor antagonist, phentolamine, with an enhancer of the nitric oxide/cyclic guanosine monophosphate pathway (L-arginine or sildenafil) on neurogenic relaxations of rabbit corpus cavernosum (RCC). METHODS: Studies were performed on isolated RCC tissue in organ chambers. Transmural electrical stimulation (TES) was applied at increasing frequencies (0.5 to 6 Hz) on endothelin-contracted RCC strips, and the responses were evaluated. RESULTS: The activation of alpha(2)-adrenergic receptors with UK 14304 (0.3 microM) significantly inhibited the relaxation induced by TES in RCC strips in which adrenergic neurotransmission was blocked with guanethidine (10 microM). The relaxant responses produced by TES application on RCC strips without guanethidine were not significantly affected by the treatment with L-arginine or sildenafil but were significantly augmented by phentolamine (2.7-fold increase in maximum relaxation). Furthermore, the combinations of phentolamine with L-arginine or sildenafil markedly increased the relaxations evoked by the application of TES in RCC tissue, significantly more than those obtained in the presence of phentolamine alone (4.5 or 4.7-fold increase of maximum relaxation, respectively). CONCLUSIONS: Our results demonstrated a synergistic interaction between the alpha-adrenergic blockade and the potentiation of the nitric oxide/cyclic guanosine monophosphate pathway to increase neurogenic relaxation of trabecular smooth muscle relaxation. This fact suggests that the combination of alpha-adrenergic receptor blockade with L-arginine or sildenafil could represent a therapeutic advantage in the treatment of erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

The use of phentolamine in the prevention of dopamine-induced tissue extravasation.

PURPOSE: The purpose of this study was to determine whether dopamine-induced tissue extravasation injury could be prevented with phentolamine. MATERIALS AND METHODS: This was a prospective, randomized, blinded, and controlled animal study. Forty rats were evaluated to document the effects of dopamine compared with normal saline on tissue integrity, whether any tissue damage was concentration or volume dependent, and to determine the minimum concentration of dopamine resulting in tissue injury. Dopamine concentrations of 0.8 mg/mL and 3.2 mg/mL were tested. In a second part of this study, an additional 40 rats were evaluated to assess the efficacy of two different doses of phentolamine (0.5 mg and 1 mg) or normal saline, when injected within 10 minutes of dopamine administration to prevent or reverse tissue extravasation. Extravasation sites were evaluated clinically and histologically at 2, 4, 6, and 8 hours and were compared with a baseline sample. Outcome measures were as follows: (1) prebiopsy was ectodermal erythema, induration, and blanching; (2) postbiopsy was bubbling, darkening, pallor, and hematoma of the muscle fascia. Histology included neutrophil migration, mast cell degranulation, edema, and hemorrhage. Fisher's Exact Test with the Bonferroni method were used for statistical analysis. RESULTS: Dopamine-induced extravasation resulted in tissue injury characterized by blanching and hematoma. Damage did not appear to be volume dependent, but may be related to the duration of infiltration. Subcutaneous injection with either dose of phentolamine appeared to be clinically effective in preventing tissue injury. However, microscopic evaluation of tissue samples was inconclusive. CONCLUSION: This study clinically supported the use of phentolamine for the prevention of dopamine-induced extravasation injury.

Adrenergic alpha-Antagonists↗
PubMed1999

Effects of phentolamine on tissue perfusion in pediatric cardiac surgery.

OBJECTIVE: To evaluate whether the deleterious effects of cardiopulmonary bypass (CPB) can be overcome by phentolamine-induced pharmacologic vasodilation in pediatric patients with congenital heart disease. DESIGN: Prospective, randomized, clinical study. SETTING: Single university hospital. PARTICIPANTS: Forty-three pediatric patients undergoing open cardiac surgery for repair of congenital heart disease. INTERVENTIONS: Patients were randomly allocated into two groups. Patients in group 1 (n = 22) received 0.2 mg/kg of phentolamine during the cooling and rewarming periods of CPB. Group 2 patients (n = 21) did not receive phentolamine. Temperature measurements (rectal [R], nasopharyngeal [N], and toe [P]) and serum lactate values were obtained before, during, and after CPB; systemic oxygen consumption was evaluated during CPB. MEASUREMENTS AND MAIN RESULTS: At the end of the CPB period and at the end of the operation, lactate values of group 1 (1.87+/-0.37 and 1.8+/-0.39 mmol/L, respectively) were significantly lower than values of group 2 (2.24+/-0.28 and 2.33+/-0.33 mmol/L; p < 0.05 and p < 0.05, respectively). At the beginning of the rewarming period N-R temperature gradients of group 1 (0.14 degrees C+/-0.92 degrees C) were lower than group 2 (-0.58 degrees C+/-1.84 degrees C) values (p < 0.05). Central-peripheral temperature gradients of group 1 obtained at the end of the CPB period (N-R = 2.18 degrees C+/-0.69 degrees C; N-P = 7.84 degrees C+/-1.54 degrees C; R-P = 5.66 degrees C+/-1.70 degrees C) were significantly lower than the values of group 2 (N-R = 2.80 degrees C+/-0.91 degrees C, N-P = 9.97 degrees C+/-2.02 degrees C; R-P = 7.18 degrees C+/-2.10 degrees C; p < 0.05; p < 0.001; p < 0.05). At the end of the operation values of group 1 (N-R = 0.48 degrees C+/-0.31 degrees C; N-P = 6.30 degrees C+/-1.23 degrees C; R-P = 5.82 degrees C+/-1.16 degrees C) were significantly lower than the values of group 2 (N-R = 0.94 degrees C+/-0.56 degrees C; N-P = 8.69 degrees C+/-0.28 degrees C; R-P = 7.75 degrees C+/-2.15 degrees C; p < 0.05; p < 0.001; p < 0.001). The systemic oxygen consumption values of group 1 were higher than group 2 (6.26+/-1.82 v 5.17+/-1.05 mL/min/kg; p < 0.05) after complete rewarming. Mean arterial pressure (MAP) values of group 1 (58.9+/-6.4 mmHg) were lower than group 2 (63.4+/-6.7 mmHg) at the period after CPB (p = 0.03). CONCLUSION: The results suggest that the use of phentolamine during CPB is associated with limited systemic anaerobic metabolism and more uniform body perfusion.

Adrenergic alpha-Agonists↗
PubMed2001

Effects of oral phentolamine, taken before sleep, on nocturnal erectile activity: a double-blind, placebo-controlled, crossover study.

The objective of this study was to determine the effects of oral phentolamine, administered before sleep, on nocturnal penile erectile activity of men with mild to moderate erectile dysfunction (ED). We studied five patients with mild to moderate ED (mean age 34.8 +/- 8.13 and mean duration of ED 31.8 +/- 23.5 months), in a double-blind, placebo-controlled, crossover study. All patients received oral phentolamine (Vasomax) at a dose of 40 mg and placebo for three consecutive nights respectively and were submitted to nocturnal penile tumescence and rigidity monitoring (NPTR) with the Rigiscan device. NPTR parameters of the two 3-night recordings were evaluated and compared. Administration of oral phentolamine before sleep was associated with a statistically significant increase in the number of erectile events with rigidity > or = 60% lasting > or = 10 min (P = 0.02), as well as the rigidity activity units (RAU) value per hour sleep, both at the base (P = 0.023) and the tip of the penis (P = 0.019). The number of events as measured by Rigiscan software (20% change in circumference), as well as tumescence activity units (TAU)/h values did not show any statistical difference. No adverse effects were recorded. It is concluded that oral phentolamine administered before sleep enhanced NPTR parameters associated with the quality of the erectile events. Such results provide a pathway for the development of a prevention strategy for ED. Future studies will elucidate whether vasoactive agents taken on a regular basis before sleep, can prevent ED in men at risk, protecting also minimally and moderately impotent patients to become moderately and severely impotent respectively.

Administration, Oral↗
PubMed2000

In vitro effects of sildenafil and phentolamine, drugs used for erectile dysfunction, on human sperm motility.

OBJECTIVE: The aim of this study was to determine the effects of sildenafil and phentolamine on sperm motility in vitro. STUDY DESIGN: Semen or washed sperm was mixed with various doses of sildenafil or phentolamine and analyzed for motility during a 30-minute period. The pH was measured for each of the samples tested. Statistical analyses were performed with analysis of variance. RESULTS: A 200-microg/mL dose of sildenafil had no effect on sperm motility. However, the highest dose (2000 microg/mL) significantly reduced motility by about 50%. The pH was reduced in this high-dose sample. The lowest dose of phentolamine (20 microg/mL) had no effect, whereas a dose of 200 microg/mL resulted in a significant reduction in sperm motility. The highest dose (2000 microg/mL) stopped virtually all sperm from moving. CONCLUSION: This study demonstrated a direct dose-related effect of phentolamine on reducing sperm motility. Only the highest dose of sildenafil had an effect, which may have been caused by a decline in pH.

Dose-Response Relationship, Drug↗
PubMed2001

Phentolamine inhibits exocytosis of glucagon by Gi2 protein-dependent activation of calcineurin in rat pancreatic alpha -cells.

Capacitance measurements were used to investigate the molecular mechanisms by which imidazoline compounds inhibit glucagon release in rat pancreatic alpha-cells. The imidazoline compound phentolamine reversibly decreased depolarization-evoked exocytosis >80% without affecting the whole-cell Ca(2+) current. During intracellular application through the recording pipette, phentolamine produced a concentration-dependent decrease in the rate of exocytosis (IC(50) = 9.7 microm). Another imidazoline compound, RX871024, exhibited similar effects on exocytosis (IC(50) = 13 microm). These actions were dependent on activation of pertussis toxin-sensitive G(i2) proteins but were not associated with stimulation of ATP-sensitive K(+) channels or adenylate cyclase activity. The inhibitory effect of phentolamine on exocytosis resulted from activation of the protein phosphatase calcineurin and was abolished by cyclosporin A and deltamethrin. Exocytosis was not affected by intracellular application of specific alpha(2), I(1), and I(2) ligands. Phentolamine reduced glucagon release (IC(50) = 1.2 microm) from intact islets by 40%, an effect abolished by pertussis toxin, cyclosporin A, and deltamethrin. These data suggest that imidazoline compounds inhibit glucagon secretion via G(i2)-dependent activation of calcineurin in the pancreatic alpha-cell. The imidazoline binding site is likely to be localized intracellularly and probably closely associated with the secretory granules.

Adenylate Cyclase Toxin↗
PubMedDate not supplied

Oral phentolamine and female sexual arousal disorder: a pilot study.

Female sexual arousal disorder (FSAD) is a highly prevalent problem, although little is known about pathophysiology or treatment of the disorder. Given the potential role of vascular mechanisms, a small pilot study was conducted on the effects of oral phentolamine in menopausal women with FSAD. Six postmenopausal women with a lack of lubrication and with sexual arousal difficulties of at least 6 months duration participated in the study. All subjects received a single dose of oral phentolamine (40 mg) and placebo in a single-blind, dose-escalation design. Dependent variables for the study included vaginal pulse amplitude (VPA), as measured by vaginal photoplethysmography, self-report measures of sexual response, and patient- and physician-based assessments of adverse events. Results indicated a mild, positive effect of phentolamine across all measures of arousal, with significant changes (p < .05) in self-reported lubrication and pleasurable sensations in the vagina. The drug was well tolerated, overall, with few reports of adverse side effects. Further studies are needed to assess the potential value of phentolamine and other vasoactive agents in the treatment of female sexual dysfunction.

Administration, Oral↗
PubMed1991

Systemic alpha-adrenergic blockade with phentolamine: a diagnostic test for sympathetically maintained pain.

The diagnosis of sympathetically maintained pain (SMP) is typically established by assessment of pain relief during local anesthetic blockade of the sympathetic ganglia that innervate the painful body part. To determine if systemic alpha-adrenergic blockade with phentolamine can be used to diagnose SMP, we compared the effects on pain of local anesthetic sympathetic ganglion blocks (LASB) and phentolamine blocks (PhB) in 20 patients with chronic pain and hyperalgesia that were suspected to be sympathetically maintained. The blocks were done in random order on separate days. Patients rated the intensity of ongoing and stimulus-evoked pain every 5 min before, during, and after the LASB and PhB. Patients and the investigator assessing pain levels were blinded to the time of intravenous administration of phentolamine (total dose 25-35 mg). The pain relief achieved by LASB and PhB correlated closely (r = 0.84), and there was no significant difference in the maximum pain relief achieved with the two blocks (t = 0.19, P greater than 0.8). Nine patients experienced a greater than 50% relief of pain and hyperalgesia from both LASB and PhB and were considered to have a clinically significant component of SMP. We conclude that alpha-adrenergic blockade with intravenous phentolamine is a sensitive alternative test to identify patients with SMP.

Adult↗
PubMedDate not supplied

Hemodynamic consequences of administration of phentolamine or nitroprusside with dopamine in the dog.

Dopamine was administered intravenously to two groups of anesthetized dogs at rates of 2.5, 5, 10 and 20 micrograms/kg/min. After the 20 micrograms/kg/min infusion, mean arterial pressure, heart rate, renal blood flow, mean pulmonary arterial pressure, and left ventricular filling pressure were increased. The dopamine infusion was continued in both groups of animals. In Group I phentolamine was administered at rates of 2.5, 5, and 7.5 micrograms/kg/min; in Group II sodium nitroprusside at rates of 1, 2, 3, and 4 micrograms/kg/min. Phentolamine and sodium nitroprusside produced similar reductions in mean arterial blood pressure, mean pulmonary arterial pressure, left ventricular filling pressure, and similar increments in heart rate. Renal blood flow was maintained with phentolamine infusions and decreased slightly with the nitroprusside infusions. These studies demonstrated that both phentolamine and nitroprusside have the ability to reduce the vasoconstricting effects of dopamine.

Animals↗
PubMedDate not supplied

Effects of two alpha-adrenoceptor antagonists, nicergoline and phentolamine, on myocardial oxygen consumption in the dog.

We compared the effects of two alpha-adrenoceptor antagonists, nicergoline and phentolamine, on myocardial oxygen consumption (MVO2) in open-chest dogs. Intravenous nicergoline, 2 micrograms/kg/min for 30 min, reduced blood pressure from 130 +/- 6 to 100 +/- 2 mm Hg, did not change heart rate, and reduced MVO2/beat from 63.1 +/- 6.6 to 43.6 +/- 4.0 microliters (p less than 0.05, compared with control saline-infused and phentolamine-treated dogs). Intravenous phentolamine, 8 micrograms/kg/min, reduced blood pressure from 123 +/- 6 to 95 +/- 8 mm Hg and increased heart rate from 199 +/- 4 to 235 +/- 9 beats/min ( p less than 0.05, compared with control and nicergoline-treated dogs). MVO2/beat did not change, but MVO2 increased from 11.1 +/- 1.5 to 13.1 +/- 2.0 ml/min (p less than 0.05, compared with nicergoline-treated dogs). These results suggest that nicergoline may be preferable to phentolamine in patients in whom it is important to avoid any increase in MVO2.

Adrenergic alpha-Antagonists↗
PubMed1977

The influence of phentolamine, an adrenergic blocking agent, on insulin secretion during surgery.

A rapid intravenous glucose load (20 g) was given with a phentolamine infusion during and after elective abdominal surgery. Plasma levels of glucose, free fatty acids, and insulin were measured to investigate the influence of surgical stress on insulin secretion. When Ringer's lactate solution was infused into a control group of subjects during surgery, plasma levels of insulin did not change during and after the surgery while plasma levels of glucose and free fatty acids increased gradually during this period. Similar results were also noted in another control group in whom only Ringer's lactate solution and phentolamine had been infused. This evidence suggests that insulin secretion responding to endogenous hyperglycemia is suppressed during surgery. In the group which was given the glucose load during infusion of only Ringer's lactate solution, plasma levels of insulin significantly increased soon after the glucose load and the gradually decreased. In another group which was given the glucose load during infusion of Ringer's lactate and phentolamine, plasma levels of insulin also increased significantly after the glucose load and remained elevated during surgery. The maximum increment of plasma insulin after the glucose load in the latter group was significantly higher than that in the former group. From these results it is suggested that suppression of insulin secretion by surgical stress is inhibited by the alpha blocking agent phentolamine.

Adult↗
PubMed1997

Intravenous phentolamine test--an aid in the evaluation of patients with persistent pain after low-back surgery?

BACKGROUND: Persistent pain following surgery in the treatment of chronic low-back pain patients is still relatively frequent. Most of these patients with persistent pain have clinical signs of neuropathic pain. The neuropathic pain might be sympathetically maintained pain (SMP) or sympathetically independent pain (SIP). Systemic administration of phentolamine, a competitive alpha-adrenergic antagonist, has been used as a diagnostic tool to identify patients with SMP. METHODS: Thirty-seven patients with persistent pain after low-back surgery (lumbar laminectomy, with or without discectomi, or a posterior fusion, with or without decompression) received intravenous phentolamine (0.5 mg/kg over 30 min) in a single-blind, placebo-controlled manner. Prior to this infusion the patients were classified clinically into different pain groups based on physical examination and imaging findings. An opioid epidural test blockade was used as a control. RESULTS: Clinical classification divided the patients into nociceptive pain (n = 7), neuropathic pain (n = 22) and mixed pain (n = 8). In the phentolamine test there were only one responder, 34 non-responders and 2 patients were placebo-responders. In the control epidural blockade there were 11 non-responders, 23 fentanyl/local anaesthetic-responders and 3 placebo-responders. CONCLUSIONS: SMP is either an uncommon cause of persistent pain in this type of failed back surgery patients or the phentolamine test, as we performed it, was unable to identify SMP.

Adrenergic alpha-Antagonists↗
PubMed2001

Effects of regional phentolamine on hypoxic vasodilatation in healthy humans.

1. Limb vascular beds exhibit a graded dilatation in response to hypoxia despite increased sympathetic vasoconstrictor nerve activity. We investigated the extent to which sympathetic vasoconstriction can mask hypoxic vasodilatation and assessed the relative contributions of beta-adrenergic and nitric oxide (NO) pathways to hypoxic vasodilatation. 2. We measured forearm blood flow responses (plethysmography) to isocapnic hypoxia (arterial saturation approximately 85%) in eight healthy men and women (18-26 years) after selective alpha-adrenergic blockade (phentolamine) of one forearm. Subsequently, we measured hypoxic responses after combined alpha- and beta-adrenergic blockade (phentolamine and propranolol) and after combined alpha- and beta-adrenergic blockade coupled with NO synthase inhibition (N(G)-monomethyl-L-arginine, L-NMMA). 3. Hypoxia increased forearm vascular conductance by 49.0 +/- 13.5% after phentolamine (compared to +16.8 +/- 7.0% in the control arm without phentolamine, P < 0.05). After addition of propranolol, the forearm vascular conductance response to hypoxia was reduced by approximately 50%, but dilatation was still present (+24.7 +/- 7.0%, P < 0.05 vs. normoxia). When L-NMMA was added, there was no further reduction in the forearm vascular conductance response to hypoxia (+28.2 +/- 4.0%, P < 0.05 vs. normoxia). 4. Thus, selective regional alpha-adrenergic blockade unmasked a greater hypoxic vasodilatation than occurs in the presence of functional sympathetic nervous system responses to hypoxia. Furthermore, approximately half of the hypoxic vasodilatation in the forearm appears to be mediated by beta-adrenergic receptor-mediated pathways. Finally, since considerable dilatation persists in the presence of both beta-adrenergic blockade and NO synthase inhibition, it is likely that an additional vasodilator mechanism is activated by hypoxia in humans.

Adrenergic alpha-Antagonists↗